EP2037975B1 - Tubes de collagene - Google Patents

Tubes de collagene Download PDF

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Publication number
EP2037975B1
EP2037975B1 EP07729978.2A EP07729978A EP2037975B1 EP 2037975 B1 EP2037975 B1 EP 2037975B1 EP 07729978 A EP07729978 A EP 07729978A EP 2037975 B1 EP2037975 B1 EP 2037975B1
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EP
European Patent Office
Prior art keywords
collagen
tube
tubes
bundle
films
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP07729978.2A
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German (de)
English (en)
French (fr)
Other versions
EP2037975A2 (fr
Inventor
Christian Gagnieu
Vincent Guyot
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Orthomed SARL
Original Assignee
Orthomed SARL
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Publication date
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Priority to PL07729978T priority Critical patent/PL2037975T3/pl
Publication of EP2037975A2 publication Critical patent/EP2037975A2/fr
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Publication of EP2037975B1 publication Critical patent/EP2037975B1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
    • Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
    • Y10T428/139—Open-ended, self-supporting conduit, cylinder, or tube-type article
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
    • Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
    • Y10T428/139—Open-ended, self-supporting conduit, cylinder, or tube-type article
    • Y10T428/1393—Multilayer [continuous layer]

Definitions

  • the present invention relates to tubes, bundles of tubes and combinations of tubes and bundles, composed of collagen, intended to be used in biology and medicine as a support for growth and / or differentiation of cellular structures, and in particular in surgery to promote the regrowth of severed nerves.
  • the invention also relates to a method of manufacturing continuous collagen films, cylindrical and coaxial, the succession of which constitutes the walls of said tubes.
  • a common technique is to surgically apply a tube connecting the two ends of the severed nerve, to guide the regrowth of the proximal portion of the nerve to the distal portion to allow their joining.
  • the tube is composed of a resorbable material.
  • Collagen is a material particularly well suited for surgical implants; it has various physicochemical and biological properties that make it a material of choice for the manufacture of tubes meeting the characteristics listed above.
  • Collagen is biocompatible and resorbable. It is possible to finely modulate its resorption rate, as well as to associate factors promoting nerve regrowth. In addition, it has low antigenicity, a role in cell growth and differentiation, and a high hemostatic potency.
  • Collagen molecules are animal proteins located in the extracellular matrix that possess in their structure one or more triple helix domains.
  • the triple helix is obtained by combining three alpha chains each composed of 1050 amino acids.
  • non-helical zones of about forty amino acids, the telopeptides allow the association of the collagen molecules with each other. This ordered arrangement of the macromolecules between them allows the formation of fibers.
  • the patent EP 0 156 740 ( US 4,814,120 ) describes a method of manufacturing collagen tubes that can be used in the field of vascular prostheses and nerve sutures. These tubes consist of a single layer of collagen.
  • Licences US 4,963,146 and US 5,026,381 describe a tube for the regeneration of severed nerves, consisting of at least two layers of collagen I having different permeabilities, including a porous outer layer.
  • the patent US 6,090,117 claims a tube to regenerate a portion of missing nerve.
  • the membrane of this tube is covered with two inner and outer layers, composed of gelatin or collagen.
  • This tube promotes the infiltration of blood capillaries.
  • the tube is filled with a "body” of collagen, including cavities, themselves filled with gel-matrix composed of collagen, laminin, proteoglycans and growth factors.
  • the patent US 6,716,225 (request WO 2003/011149 ) describes a tubular matrix composed of collagen.
  • the matrix has an inside diameter of between 0.1 and 10 mm.
  • the outer wall of this matrix is characterized by its roughness.
  • the patent US 6,953,482 describes an instrument used to promote nerve regeneration, consisting of a tube-shaped support, a sponge matrix filling the tube, and a tubular structure made of collagen fibers, to guide the regrowth nerve.
  • the patent application US 2004/0170664 discloses a tube for use in neuronal regeneration, consisting of a resorbable outer wall, smooth and non-porous. This wall is composed of a single collagen film folded on itself, the two ends being welded or glued. The tube can be filled with a collagen matrix.
  • the document US 3,562,820 describes a succession of layers of mucosa glued to each other by a fibrous collagen glue.
  • the layers are a non-homogeneous composite mixture.
  • the invention described in the document WO82 / 03764 consists of a plurality of collagen-containing layers in association with living cells responsible for collagen molecular array.
  • the document EP 0943345 discloses a succession of nonwoven collagen layers randomly formed at the time of freezing and dehydration under vacuum.
  • the tubes have a rough wall, it can injure the surrounding tissue.
  • the presence of welding or bonding zones on the outer membrane is a disadvantage because these asperities are irritating.
  • the presence of matrix in the tubes does not effectively guide the nerve regrowth.
  • the present invention therefore proposes a new type of collagen tube. intended to be used for the regeneration of a nerve, in which is inserted a bundle of tubules, welded together, for individually guiding the progression of fascicles of axons, components of the nerve.
  • Each tube and tubule consists of a succession of continuous collagen films, cylindrical and coaxial, and preferably having substantially the same porosity.
  • the present invention relates to a collagen tube for the regeneration of a nerve characterized in that it comprises a wall consisting of a succession of continuous collagen films. circular cylindrical and coaxial.
  • continuous film is meant that the film is in one piece and does not contain a welding or bonding zone.
  • These films are in the form of a substantially cylindrical tube.
  • the term "cylindrical tube” means all cylinders from a director, preferably a circular director.
  • the coaxial qualifier indicates that all assembled films share the same axis, which is the axis of the tube.
  • These films are advantageously transparent, homogeneous and contain little or no aggregates.
  • These films are preferably non-porous, that is to say that there is no porosity greater than 1 micron.
  • the diffusion of molecular weight molecules of about 70 kDa to through the wall of the tube is possible.
  • the average resorption time of the tube is controllable and variable according to the treatments.
  • each collagen film constituting the wall has a thickness of between 0.5 and 4 ⁇ m.
  • the invention relates more particularly to a collagen tube, the wall of which consists of a succession of at least 5 continuous, cylindrical and coaxial collagen films.
  • the wall is constituted by a succession of 5 to 30 films, and in particular from 10 to 15 films.
  • the films assembled to form the wall of a tube can all be of the same composition.
  • the films constituting the same wall may have different compositions, that is to say be composed of different types or mixtures of collagens.
  • the films constituting the inner and outer layers may be composed of different mixtures of collagen.
  • the films forming the walls may contain collagen I, collagen III, or a mixture of both.
  • the mixture can comprise all the possible relative proportions of collagens I and III.
  • the preferred composition is a mixture comprising 85 to 100% collagen I and 0 to 15% collagen III.
  • the films may comprise collagen IV, either pure or combined with other types of collagen, in all the possible relative proportions.
  • the preferred composition is a mixture comprising from 1 to 100% by weight of collagen IV and from 0 to 99% by weight of collagen I, or a mixture of collagen I + III in the proportions described above.
  • the films constituting the innermost part of the wall comprise collagen IV, the other more external films being constituted by collagen I or a mixture of collagens I and III.
  • the collagens used may be from several species, in particular from the bovine or porcine species.
  • the collagen used is atelocollagen, that is to say a collagen which has undergone cleavage at the level of telopeptides (Rousseau & Gagnieu, Biomaterials, 2002).
  • the collagen constituting the walls of the tubes is crosslinked.
  • the crosslinking is done by conventional techniques known to those skilled in the art. It can be done for example under the action of radiation.
  • the crosslinking reaction will be carried out by dipping the collagen tube in a solution of formaldehyde, at a concentration of between 0.01 and 2%, for a time of between 1 minute and 72 hours, at a pH of between 3 and 9, 5, these factors being adapted according to the desired degree of crosslinking.
  • the collagen tube according to the invention can be used for all kinds of application. It is particularly intended for use in neural surgery, to guide and protect a sectioned nerve during regrowth.
  • the section of the collagen tube is adapted to the section of the nerve that must be guided in its regrowth: ideally the inside diameter of the tube should be equal to the section of the nerve to be regenerated.
  • the inside diameter of the collagen tube according to the invention is between 50 ⁇ m and 10 mm. Preferably it is between 1 and 7 mm.
  • the invention also relates to small diameter tubes, hereinafter called tubules, which have an internal diameter less than or equal to 500 microns, and which is preferably between 50 and 200 microns, and preferably 100 microns.
  • the invention also relates to a bundle of collagen tubes characterized in that it comprises at least two tubes according to the invention, aligned in parallel and welded to each other.
  • the tubes forming the bundle are all of the same length and have the same internal diameter.
  • the tubes constituting the bundle have an internal diameter of less than 500 ⁇ m, and more preferentially an internal diameter of between 50 and 200 ⁇ m. They are then called “tubules”.
  • the welding of the tubes or tubules is carried out by partial melting of the outer membranes of said tubes.
  • Those skilled in the art will be able to determine the optimal parameters of the fusion reaction to obtain a partial melting of the outer membranes.
  • the beam can be composed of a number of tubes or tubules comprised between 2 and 60, and in particular be composed of 2, 3, 4, 5, 10, 15, 20, 30, 40, 50 or 60 tubules, depending the diameter of the beam that is desired.
  • This bundle is also characterized in that it is wrapped with a collagen sheath.
  • This sheath has a thickness of between 1 and 3 ⁇ m. This coating of the beam makes it possible to give it a smooth and homogeneous surface, which facilitates insertion of the beam into a tube, where appropriate.
  • This sheath is preferably predominantly composed of type I collagen.
  • the bundle thus formed is advantageously subjected to a crosslinking reaction, after assembly and welding of the tubules together, then sheathing by a film of collagen.
  • the crosslinking can be carried out according to all the conventional techniques known to those skilled in the art, and in particular will be carried out using a formaldehyde solution as described above.
  • the present invention also relates to a combination of tubes characterized in that it comprises a tube according to the invention, in which is inserted longitudinally at least one bundle of tubes according to the invention.
  • the respective diameters of the beam and the tube are adapted to be able to be combined.
  • the beam (s) are inserted into the tube in the dry state.
  • the tubes and tubules according to the invention may have all the possible lengths; in general, a tube of suitable length is prepared which is then cut to the desired length by conventional techniques known to those skilled in the art.
  • the length of the tube and the beam will be adapted to the length of the missing nerve section.
  • the sectioned nerves have a lack of nerve substance of the order of a few centimeters, which can reach 15 cm.
  • the length of the missing substance is 2.5 to 3 cm.
  • the loss of substance may be 10 to 15 cm.
  • the length of the tube is between 5 mm and 10 cm.
  • the tube or the combination of tubes according to the invention In order for the tube or the combination of tubes according to the invention to effectively protect the zone to be regenerated as well as the two ends of the nerve to be repaired, it is preferable for the tube to be longer than the zone to be regenerated.
  • the length of the tube used is greater than the length of the loss of nerve substance to allow, in particular, the suture of the nerve endings cut in the tube. This additional length is advantageously about 6 mm, which leaves 3 mm on each side to allow the suture and ensure good protection of the ends.
  • the tube / beam combination according to the invention is characterized in that the length of the tube is greater than the length of the beam; in particular, the beam will have the length of the loss of nerve substance, and the tube will have a longer length to ensure the protection of the suture and the ends, preferably 6 mm more, or 3 mm on each side of the area to be regenerated .
  • the tube containing the bundle of tubules will be sutured to the extremities of the nerve by the practitioner.
  • the nerve to reconstruct it is first dissected with the naked eye and then under a microscope, the ends are intersected until finding a "healthy" zone at the level of the two stumps, then the guardian is put in place using several points of microscopic suture.
  • Proximal and distal sutures can be "reinforced" with biological glue.
  • the present invention also relates to a method of manufacturing a collagen tube as defined above, in which the collagen is solubilized in a suitable solvent, the solution obtained is deposited on a cylindrically shaped support and then dried, these two steps being repeated. to obtain a succession of continuous, concentric and coaxial collagen films.
  • aqueous solvents conventionally used to dissolve collagen have a rather slow evaporation, which favors the formation of aggregate.
  • the collagen when it is dissolved in a suitable organic solvent, it can be evaporated at a rate sufficient to prevent the formation of aggregates.
  • the solvent is a polar solvent.
  • the solvent contains glycerol. The dissolution of the collagen in this solution is carried out with stirring for a few hours.
  • the solvent contains methanol, and is preferably a mixture of methanol and water (30-100% methanol, water 0-70% by volume) or pure methanol 98-100%.
  • All forms of collagen can be used: acid-soluble collagen, fibrous collagen, atelocollagen or denatured collagen.
  • the preferred form is atelocollagen at a high purity level (about 99%).
  • This method has the advantage that the drying time is 5 minutes for a 1.5 mm ID tube; this value may increase depending on the diameter of the tube, but the incrementation of the drying time will be of the order of one minute. For an equivalent process using an aqueous solution, the drying time would be greater than one hour.
  • the diluted collagen solution preferably contains a surfactant compound, which will be removed by the subsequent washing of the tubule.
  • a surfactant compound which will be removed by the subsequent washing of the tubule.
  • the cylindrical support is a smooth-surfaced synthetic polymer tube having a diameter equal to the desired inner diameter for the tube.
  • the support is made of PTFE.
  • the dissolved collagen solution is deposited by immersing the support in the solution. Between each dipping, the tube is dried under a de-dusted air stream.
  • the steps of immersion of the support and drying will be repeated as many times as it is desired to assemble films; in particular the steps will be repeated between 5 and 30 times to obtain a tube whose wall consists of a succession of 5 to 30 films.
  • the collagen of the tubes will then preferably be subjected to a crosslinking step.
  • the cylindrical support will be removed after this crosslinking step.
  • the collagen tube formed by the succession of dipping / drying steps is then immersed in a pH-controlled formalin solution, then in water, then in a glycine solution and then in water, and finally in acetone, before demolding the tubes.
  • the invention also relates to any collagen film that can be obtained according to the process as previously described.
  • this film has the characteristics of being transparent, perfectly homogeneous and containing no or few aggregates.
  • a bundle of tubules To prepare a bundle of tubules, the latter always containing the support are assembled longitudinally.
  • the bundle of tubules thus obtained is immersed in a suitable solvent allowing the swelling and the partial dissolution of the outermost layers of each tubule.
  • the beam thus treated is subjected to a weak longitudinal force allowing a rimpedement of the tubules and a melting of the layers being solubilized.
  • the rapid drying under air flow of the beam ensures the solidification of the fused zones and thus the welding of the tubules between them.
  • the bundle After drying, the bundle is surrounded by a collagen film and then subjected to a collagen crosslinking step. The molds are removed after crosslinking.
  • the crosslinking of the collagen is carried out in the following manner: immersion of the bundle in a pH-controlled formalin solution as previously described, then successive immersion in water, 0.1M glycine, water and acetone.
  • the present invention relates to a collagen tube or a bundle of tubes or an association of collagen tubes according to the invention, for its use in surgery.
  • the invention also relates to the use of a tube or bundle of tubes or a combination of tubes, for the preparation of a surgical device for promoting and guiding the regrowth of a severed nerve.
  • the tubes according to the invention are particularly suitable for neurosurgery because they can be used for the preparation of a surgical device for promoting and guiding the regrowth of a nerve that has been sectioned.
  • the collagen tube or the combination of tubes according to the invention may serve as "tutors" allowing two nerve ends severed or damaged in any way to meet and reconnect. This technique can be applied to both motor nerves and sensitive fibers.
  • a collagen solution is prepared by dissolving 0.25 g of collagen in 50 ml of methanol containing glycerol at a concentration corresponding to 50-100% of the final concentration of collagen.
  • the solution obtained is homogenized by successive extrusions through sieves of mesh 150 and 50 .mu.m.
  • a cylindrical and rectilinear PTFE mold with a diameter of between 500 .mu.m and 10 mm is immersed in the collagen solution and removed after 2-15 seconds of waiting at a speed of between 0.5 and 2 cm per second.
  • the mold coated with collagen solution is then rotated in a stream of filtered air for 2 to 15 minutes to obtain a homogeneous evaporation of the solvent.
  • the soaking and drying operations are performed from 2 to 30 times depending on the number of collagen layers desired. After the last soaking, the final drying is carried out for 15 minutes.
  • the crosslinking of the collagen is obtained by immersing the mold supporting the collagen layers in a 0.01-0.5% formaldehyde bath for a time varying between 5 minutes and 24 hours. It is then immersed successively for 5 minutes in a water bath, 5-60 minutes in a 0.1M glycine bath, 30 minutes in a water bath and then 5-15 minutes in acetone. After evaporation of the acetone for 5-15 minutes in a stream of filtered air, the PTFE mold is removed to give a crosslinked multilayer collagen tube which is placed at least 16 hours in a drying chamber for final drying up to a humidity level of less than or equal to 15%. According to this method, tubes of 3 to 25 cm are obtained.
  • the collagen solution is prepared as above but additionally contains 0.5% (v / v) of a surfactant product such as Tween 20.
  • This solution is filtered 3 times on a 50 ⁇ m sieve.
  • PTFE molds with a diameter of 50-200 ⁇ m are immersed in 1-5 seconds in this solution and the withdrawal is carried out at a speed of between 3 and 10 centimeters per second.
  • Evaporation of the solvent is carried out by exposing the collagen-coated mold for 5 minutes under an air stream. The operation can be performed from 2 to 30 times.
  • the tubules supported by their PTFE molds are combined into bundles of 3 to 60 parallel units and the bundles are ligated to the ends.
  • These beams are then immersed without traction for 2 to 20 seconds in a bath of methanol, then they are subjected to a small longitudinal traction to bring the tubules in close contact with each other, this operation being followed by a drying of 5 minutes. at 15 minutes under airflow.
  • the resulting beam is coated with collagen by immersion / drying cycles (1 to 5) in a methanolic solution of collagen at a concentration of 0.1-0.5% containing 0.25% glycerol.
  • the beams obtained are crosslinked, demolded and dried according to the process described in the manufacture of outer tubes / envelopes. According to this method, bundles of 3 to 60 tubules are obtained.
  • the assembly of the two elements is carried out in the dry state.
  • the diameter of the tube / envelope is greater than the diameter of the beam which is related to the number and the diameter of the tubules that it contains.
  • the beam is inserted longitudinally into the envelope. Its length may be equal to or less than that of the envelope.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Biophysics (AREA)
  • Neurology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)
  • Peptides Or Proteins (AREA)
EP07729978.2A 2006-06-22 2007-06-07 Tubes de collagene Not-in-force EP2037975B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL07729978T PL2037975T3 (pl) 2006-06-22 2007-06-07 Rurki kolagenowe

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0605610A FR2902661B1 (fr) 2006-06-22 2006-06-22 Tubes de collagene
US90714207P 2007-03-22 2007-03-22
PCT/EP2007/055614 WO2007147739A2 (fr) 2006-06-22 2007-06-07 Tubes de collagene

Publications (2)

Publication Number Publication Date
EP2037975A2 EP2037975A2 (fr) 2009-03-25
EP2037975B1 true EP2037975B1 (fr) 2014-06-18

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP07729978.2A Not-in-force EP2037975B1 (fr) 2006-06-22 2007-06-07 Tubes de collagene

Country Status (13)

Country Link
US (1) US20100221291A1 (ko)
EP (1) EP2037975B1 (ko)
JP (1) JP5089688B2 (ko)
KR (1) KR101360311B1 (ko)
BR (1) BRPI0712979A2 (ko)
CA (1) CA2655012C (ko)
DK (1) DK2037975T3 (ko)
ES (1) ES2502844T3 (ko)
FR (1) FR2902661B1 (ko)
IL (1) IL196002A (ko)
NO (1) NO20085266L (ko)
PL (1) PL2037975T3 (ko)
WO (1) WO2007147739A2 (ko)

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FR2944706B1 (fr) 2009-04-28 2012-08-24 Biom Up Nouveaux materiaux en collagene et procedes d'obtention.
KR102067676B1 (ko) * 2017-11-30 2020-01-17 한국과학기술연구원 전극을 이용한 콜라겐 섬유가 정렬된 콜라겐 튜브를 제조하는 방법

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TWI264301B (en) * 2002-03-11 2006-10-21 Ind Tech Res Inst Multi-channel bioresorbable nerve regeneration conduit and preparation method for the same
US7229971B2 (en) * 2002-03-11 2007-06-12 Japan Science And Technology Agency Regulation of biodegradability of composite biomaterials
JP4605985B2 (ja) * 2002-12-27 2011-01-05 ニプロ株式会社 神経再生誘導管

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IL196002A0 (en) 2009-09-01
WO2007147739A2 (fr) 2007-12-27
PL2037975T3 (pl) 2015-01-30
KR20090018214A (ko) 2009-02-19
CA2655012C (fr) 2014-10-28
FR2902661A1 (fr) 2007-12-28
ES2502844T3 (es) 2014-10-06
CA2655012A1 (fr) 2007-12-27
US20100221291A1 (en) 2010-09-02
NO20085266L (no) 2008-12-16
FR2902661B1 (fr) 2011-05-13
IL196002A (en) 2014-05-28
WO2007147739A3 (fr) 2008-02-21
JP5089688B2 (ja) 2012-12-05
DK2037975T3 (da) 2014-09-22
JP2009540896A (ja) 2009-11-26
EP2037975A2 (fr) 2009-03-25
BRPI0712979A2 (pt) 2012-03-27
KR101360311B1 (ko) 2014-02-11

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